TY - JOUR
T1 - Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome
AU - Yamaguchi, Hiroki
AU - Baerlocher, Gabriela M.
AU - Lansdorp, Peter M.
AU - Chanock, Stephen J.
AU - Nunez, Olga
AU - Sloand, Elaine
AU - Young, Neal S.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Mutations in the human telomerase RNA (TERC) occur in autosomal dominant dyskeratosis congenita (DKC). Because of the possibility that TERC mutations might underlie seemingly acquired forms of bone marrow failure, we examined blood samples from a large number of patients with aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplasia (MDS). Only 3 of 210 cases showed heterozygous TERC mutations: both nucleotide 305 (n305) (G>A) and n322 (G>A) were within the conserved region (CR) 4-CR5 domain; n450 (G>A) was localized to the boxH/ACA domain. However, only one patient (with a mutation at n305 [G>A]) had clinical characteristics suggesting DKC; her blood cells contained short telomeres and her sister also suffered from bone marrow failure. Another 21 patients with short telomeres did not show TERC mutations. Our results suggest that cryptic DKC, at least secondary to mutations in the TERC gene, is an improbable diagnosis in patients with otherwise typical AA, PNH, and MDS.
AB - Mutations in the human telomerase RNA (TERC) occur in autosomal dominant dyskeratosis congenita (DKC). Because of the possibility that TERC mutations might underlie seemingly acquired forms of bone marrow failure, we examined blood samples from a large number of patients with aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplasia (MDS). Only 3 of 210 cases showed heterozygous TERC mutations: both nucleotide 305 (n305) (G>A) and n322 (G>A) were within the conserved region (CR) 4-CR5 domain; n450 (G>A) was localized to the boxH/ACA domain. However, only one patient (with a mutation at n305 [G>A]) had clinical characteristics suggesting DKC; her blood cells contained short telomeres and her sister also suffered from bone marrow failure. Another 21 patients with short telomeres did not show TERC mutations. Our results suggest that cryptic DKC, at least secondary to mutations in the TERC gene, is an improbable diagnosis in patients with otherwise typical AA, PNH, and MDS.
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U2 - 10.1182/blood-2003-01-0335
DO - 10.1182/blood-2003-01-0335
M3 - Article
C2 - 12676774
AN - SCOPUS:0041592752
SN - 0006-4971
VL - 102
SP - 916
EP - 918
JO - Blood
JF - Blood
IS - 3
ER -